Grafted Immunoisolated Human Benign Insulinoma Reduces the Incidence of Diabetes in Young NOD Mice without Abolishing the Auto-Immunity

Abstract

Exogenous insulin may prevent the auto-immunity of diabetes in rodents. We studied the preventive effect of a safe endogenous insulin delivery in the diabetes-prone NOD mouse by immuno-protected human insulinoma grafts. Perm-selective macrocapsules seeded with human insulinoma were implanted in 34 young NOD mice, 4 and 8 weeks old. The animals were observed 18 months and compared to 34 NOD mice grafted with empty fibers and 25 simply observed. Before grafting, the capacity of the macrocapsules to release insulin was assessed in vitro by perifusion studies and by implantation to 12 diabetic NOD mice. At perifusion, the insulin release of the macrocapsules responded to step changes in glucose. During the in vivo study, the capsules reduced the glycemia of diabetic mice from 18±3.5 to 7.3±2.1 mmol/L. In the study groups, the survival rate without diabetes (50-70%) was statistically different from controls (10-20%). Recipient's splenocytes transplanted to irradiated male NOD mice transferred the autoimmunity in 75-83% of grafted mice and 86-100% of controls. Insulitis was persistent in all, although milder in the grafted mice. Encapsulated insulinoma prevents diabetes in the NOD mouse without abolishing the auto-immunity. The quantity and quality of the tissues needed and the best moment to graft them have to be determined. The prevention of diabetes by encapsulated pancreatic tissue is appealing because of its simplicity and safety.